U.S. Pat. No. 4,374,829 Harris et al, issued Feb. 22, 1983, and U.S. Pat. No. 4,472,380 Harris et al issued Sept. 18, 1984, both describe certain carboxyalkyl dipeptide derivatives useful as hypertensives, and processes for their preparation. Among the preferred compounds in these patents is 1-[N-[(S)]-1-carboxy-3-phenylpropyl]-L-alanyl]-L-proline 1'-ethyl ester, referred to herein as enalapril, and having the chemical formula: ##STR1## and N-1-[1(S)-carboxy-3-phenylpropyl]-L-lysyl-L-proline, referred to herein as lisinopril, and having the chemical formula: ##STR2## In the process specifically described and exemplified in the aforementioned patents [Examples 26, 43 and 57), a diaminoacid e.g. L-alanyl-L-proline or L-lysyl-L-proline, with t-butoxy-carbonyl protection of the acid function thereof, is condensed with 2-oxo-4-phenylbutyric acid, in the presence of sodium cyanoborohydride. General reference is made to an alternative process in which, in a final stage, appropriately protected proline is reacted with an esterified phenalkylamino acid.
It is known to prepare dipeptide derivatives by reaction of N-(1-carboethoxy-3-phenylpropyl)-.alpha.-aminopropionic acid, of formula: ##STR3## with appropriate amino acids, by reaction of the acid moiety thereof with the amino group of the amino acid. When a proline moiety is used as the amino acid, enalapril can be formed. When other amino acids are chosen, a variety of ACE-inhibiting compounds can be formed. Thus, the compound N-(1-carboethoxy-3-phenylpropyl)-.alpha.-aminopropionic acid, (also known as N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanine), and the similar compounds corresponding to the general formula: ##STR4## where R represents phenalkyl, R.sub.1 represents lower alkyl, phenyl or benzyl, and R.sub.2 represents lower alkyl, lower alkyl amino or N-substituted lower alkyl amino, represent valuable synthetic intermediates in the preparation of dipeptide derivative compounds.